Cardiac surgeons have long recognized the deleterious effect of ischemia and even non-ischemic cardiopulmonary bypass upon myocardial function. Although improved surgical techniques have made many cardiac abnormalities amenable to repair, patients still succumb to failing myocardial function after technically successful operations. Increasing attention is now being paid to the protection of the myocardium during the conduct of cardiac operations. Employing the isolated cross-perfused dog heart, the project outlined herein is aimed at elucidating those conditions under which maximal myocardial protection can be maintained, particularly during myocardial ischemia. A controlled injury (ischemia or pump oxygenator perfusion) will be inflicted upon the heart. After a baseline response has been established, we will modify pH, electrolyte concentration, and osmolarity. The protective effect of an acid pH upon isolated ischemic myocardial muscle, first described by the Co-investigator (Dr. O. Bing), will be tested for the first time in the intact heart. The extent of myocardial injury or protection will be measured from three different standpoints: 1) mechanical performance of the isovolumetric heart (developed pressure, LVEDP, ventricular compliance, and wall thickness); 2) myocardial metabolism and biochemistry (myocardial oxygen consumption and coronary vascular resistance; transmyocardial lactate consumption or production; changes in glycogen stores, ATP/CP stores, and myocardial enzyme content; and calcium, sodium, and potassium fluxes); 3) structure (light and electron microscopy). In the process of seeking better methods of protecting myocardial function during open heart operations, we hope to define further the pathophysiology of myocardial deterioration during cardiopulmonary bypass. In preliminary experiments, for example, we have observed changes in ventricular wall thickness, associating them for the first time in the laboratory with a contracture-like state resembling the "Stone Heart". By correlating mechanical, metabolic, and structural events associated with perioperative myocardial injury, we hope to develop a systematic means of preventing these alterations.